Carcinoid Syndrome (cont.)

Dennis Lee, MD

Dr. Lee was born in Shanghai, China, and received his college and medical training in the United States. He is fluent in English and three Chinese dialects. He graduated with chemistry departmental honors from Harvey Mudd College. He was appointed president of AOA society at UCLA School of Medicine. He underwent internal medicine residency and gastroenterology fellowship training at Cedars Sinai Medical Center.

Jay W. Marks, MD

Jay W. Marks, MD, is a board-certified internist and gastroenterologist. He graduated from Yale University School of Medicine and trained in internal medicine and gastroenterology at UCLA/Cedars-Sinai Medical Center in Los Angeles.

Since carcinoid tumors vary widely in their size, malignant potential, prognosis, extent of metastasis, and symptoms, treatment should be customized for each individual. Because the carcinoid syndrome and metastatic carcinoid tumors are rare and their treatments are complex, many patients should be treated by a team of doctors--gastroenterologists, oncologists, radiologists, cardiologists, and surgeons--in medical centers experienced and equipped to treat carcinoid tumors.

Observation

Some patients with unresectable carcinoid tumors may have neither local symptoms nor the carcinoid syndrome. These patients can be observed without surgery or medications because carcinoid tumors are slow growing, and the patients may not develop symptoms for a prolonged period of time.

Surgery

Surgery is used for 1) curative resection, 2) relief of symptoms such as small intestinal obstruction or intestinal bleeding, and 3) reducing the size of tumors that are not completely resectable, a process called tumor debulking, to decrease the tumor burden and decrease the amount of hormone produced by the tumors.

Small rectal carcinoid tumors usually are benign and often can be completely excised for cure. Type 1 gastric carcinoid tumors also usually are benign and often can be removed for cure. Small appendiceal carcinoid tumors usually are removed and cured at the time of appendectomy.

Carcinoid tumors of the small intestine and the colon often are large and have already metastasized at the time of diagnosis. Most patients with metastases are not candidates for surgical cure because surgery cannot completely remove the entire tumor. Occasionally, a patient may have a solitary metastasis confined to a portion of the liver. Such patients can be treated with surgical resection of the primary tumor and resection of that part of the liver containing the tumor (partial hepatectomy). There are a limited number of patients with multiple metastases that are confined to the liver. Partial hepatectomy cannot be performed in these patients because of the multiple locations of the tumors. A small number of these patients have been treated successfully with liver transplantation.

Cryotherapy, radiofrequency ablation, hepatic artery embolization

Cryotherapy, radiofrequency ablation, and hepatic artery embolization all are techniques for debulking unresectable tumors (mainly liver metastasis) in order to decrease tumor burden and to treat the carcinoid syndrome. Effective debulking can improve the carcinoid syndrome and also prolong survival. Probes that freeze (cryotherapy) or deliver radiofrequency waves (RF ablation) can be inserted into the liver to debulk the liver of metastases from carcinoid tumors. Hepatic artery embolization involves blocking the arterial blood supply to carcinoid tumors (using oil-gelatin sponge particles) in the liver followed by chemotherapy to debulk the remaining the liver tumors. Alternatively, radioactive microspheres can be injected into hepatic arteries to kill the liver tumors.

Interferon and chemotherapy

Interferon is a substance that inhibits the replication of some viruses and the growth of some tumors. Interferon has been used to treat patients with chronic hepatitis B and C. Interferon also has been found to arrest the growth of carcinoid tumors in some patients. Interferon has significant side effects, however.

Chemotherapy has been used alone or in combinations with other therapies to treat carcinoid tumors with metastases. The agents used include 5-fluorouracil (5-FU), cyclophosphamide, streptozotocin, and doxorubicin. The tumors do not frequently respond to treatment (a response is seen in under 20% of tumors), and the duration of response usually is only a few months. The side effects and toxicity of chemotherapy can be high.

Radiation therapy

External radiation has been used to alleviate pain due to the presence of metastases from carcinoid tumors in the spine. It also may reduce the size of the tumor in the spine. External radiation usually is not effective in treating tumors within the liver. Radioactive isotopes have also been used to palliatively treat metastatic carcinoid tumors with some benefit reported, although the seies of patients so treated have been limited.

Medications for the control of the carcinoid syndrome

The most important treatment modality for the carcinoid syndrome is octreotide, a synthetic hormone similar in structure to the naturally-occurring hormone, somatostatin. Somatostatin is widely distributed in the body where it can inhibit the secretion of many other hormones including growth hormone, insulin, and gastrin. It exerts its action by binding to specific receptors on the membranes of cells that produce and release hormones and chemical substances. Octreotide, like somatostatin, binds to receptors on the cells of carcinoid tumors and inhibits the manufacture and release of tumor hormones. Octreotide is very effective in controlling the symptoms of flushing and diarrhea that are part of the carcinoid syndrome. Octreotide has been found to reduce the excretion of 5-HIAA in some patients. Octreotide also has been found to slow the growth of carcinoid tumors, and, in a few patients, even reduce the size of the tumors and their metastases. Treatment with octreotide prior to surgery is important in order to prevent life-threatening carcinoid crisis in patients with carcinoid syndrome undergoing surgery. Some doctors are advocating using octreotide even in patients without carcinoid syndrome to control the growth of the carcinoid tumors.

Octreotide generally is well tolerated. Side effects include nausea, headache, dizziness, abdominal pain, diarrhea, elevated blood sugar levels, and gallstones. The major drawback of octreotide is the need to inject it under the skin three times daily. Other longer-acting synthetic hormones resembling somatostatin (for example, lanreotide) can be given intramuscularly every two weeks, but they are not yet available in the U. S.

Patients with carcinoid syndrome should take vitamin supplements, especially nicotinic acid, since carcinoid tumors can cause a deficiency of nicotinic acid. In some patients, diarrhea caused by the carcinoid syndrome may respond to Imodium, Lomotil, ondansetron (Zofran), or cyproheptadine (Periactin). Patients also should avoid alcohol, spicy foods, physical stress, and ephedrine-containing medications such as nasal decongestants in order to avoid the precipitation of carcinoid syndrome by the release of hormones and chemical substances from the tumor. Patients with chronic diarrhea should take minerals supplements as well as vitamins since any cause of chronic diarrhea can lead to deficiencies of minerals.